Glycosyltransferase Mechanisms in Plant Natural Product Biosynthesis

Glycosyltransferases are enzymes that catalyse the transfer of sugar moieties from activated nucleotide‐sugar donors to a wide range of acceptor molecules, thereby generating glycosides with altered solubility, stability and biological activity. In plants, these enzymes underpin the diversification of secondary metabolites such as flavonoids, terpenoids, phenylpropanoids and saponins. By modulating chemical polarity and directing subcellular localisation, glycosyltransferases regulate metabolite storage, transport and detoxification. Mechanistic studies have revealed that family 1 glycosyltransferases share a conserved Rossmann‐like fold and employ an SN2 reaction mechanism in which the sugar donor is positioned for nucleophilic attack by the acceptor hydroxyl or carbon atom. Substrate specificity is determined by a combination of active‐site residues that recognise both donor and acceptor, often via hydrogen bonds and hydrophobic contacts. Structural analyses have highlighted the plasticity of loop regions around the active site, enabling single amino acid changes to switch donor preference or acceptor scope. Such modularity underlies the rapid evolution of glycosyltransferases and their recruitment to diverse biosynthetic pathways. Practical applications include metabolic engineering of plants or microbes to produce high‐value glycosides for pharmaceuticals, colourants and flavourings, as well as the development of stress‐resilient crops through manipulation of endogenous glycosyltransferase expression.

Research from Nature Portfolio

Recent studies have elucidated a dedicated apiosyltransferase from Glycyrrhiza uralensis that catalyses 2''-O-apiosylation of flavonoid glycosides with exceptionally high selectivity for UDP-apiose. Crystal structures of the enzyme revealed a novel RLGSDH motif in the sugar-binding pocket, accounting for donor specificity. Guided by structural insights and computational modelling, targeted mutations of key residues were shown to alter sugar preference, demonstrating tunable donor recognition. Moreover, transcriptomic mining across Leguminosae identified over a hundred candidate apiosyltransferase genes, of which several were functionally characterised. Introduction of the core apiosyltransferase and upstream pathway genes into Nicotiana benthamiana enabled de novo biosynthesis of flavonoid apiosides, showcasing the potential for heterologous production of rare natural glycosides.

Glycosyltransferase Mechanisms in Plant Natural Product Biosynthesis publication trend

The graph below shows the total number of articles in glycosyltransferase mechanisms in plant natural product biosynthesis across all publications each year (not limited to Nature Index journals).

Technical terms

Glycosyltransferase: Enzyme that transfers a sugar moiety from a nucleotide‐sugar donor to an acceptor molecule, forming a glycosidic bond.

UDP-sugar: Activated sugar donor in which a sugar is linked to uridine diphosphate, serving as the substrate for glycosyltransferases.

Acceptor substrate: Molecule (often a flavonoid, terpenoid or phenolic compound) that receives a sugar moiety in a glycosylation reaction.

Rossmann fold: Protein structural motif that binds nucleotide cofactors, characterised by alternating β-strands and α-helices.

SN2 mechanism: Bimolecular nucleophilic substitution in which the nucleophile attacks the electrophile as the leaving group departs, occurring in glycosyl transfer.

Apiosyltransferase: Glycosyltransferase that specifically transfers apiose residues to acceptor compounds, forming apiosides.

Heterologous expression: Production of a gene product in an organism other than the native source, often used for pathway reconstruction.

References

1. Insights into the missing apiosylation step in flavonoid apiosides biosynthesis of Leguminosae plants. Nature Communications (2023).
2. Structural Insights into the Substrate Recognition of Ginsenoside Glycosyltransferase Pq3‐O‐UGT2. Advanced Science (2025).
3. The function of UDP-glycosyltransferases in plants and their possible use in crop protection. Biotechnology Advances (2023).
4. Advances in understanding glycosyltransferases from a structural perspective. Current Opinion in Structural Biology (2014).